This Shared Instrumentation Grant proposal seeks supplemental funds for the purchase of a 300kV field emission gun electron microscope to augment our on-going three-dimensional (3-D) structural studies of a broad range of macromolecules of biological interest. The critical need for a high-resolution cryo-electron microscope research instrument is justified at multiple levels: The high-resolution electron microscope will provide essential instrumentation for five primary users with NIB funded research that now requires structure determinations beyond 10 A resolution. The limited time available on one other suitable electron microscope in the Houston area has made it apparent to the users that our research would be greatly augmented by the acquisition of the high-resolution electron microscope. The 3-D electron microscope (3-D EM) will be an integral part of the Structural Biology Center that has recently been established at the University of Texas Medical School in Houston. The high resolution EM instrumentation together with the X-ray crystallography, 600 MHz high-resolution NMR spectrometer, and the molecular modeling expertise in the center will provide a valuable resource for faculty who want to expand the scope of their current research projects to include high resolution EM. The EM with high-resolution capabilities will meet a critical requirement of high-resolution data for ongoing software development. The diverse biological structures with their highly varied architectures offer a fertile source of data for developing and refining the methodology of high-resolution EM, which will not only benefit our efforts but also the 3-D EM community at large. The identification of seven secondary users shows that there is major interest in the larger medical school community that may greatly benefit by acquisition of the high-resolution electron microscope.